The purpose of this proposal is to examine the mechanical, neuromuscular, and reflex control of airflow in the upper airway in both humans during sleep and in an isolated canine upper airway. The major focus of this work is to elucidate underlying mechanisms in the control upper airway airflow and to determine whether specific alterations exist in the control of airflow in patients with obstructive sleep apnea. Specifically, a Starling resistor model of the upper airway will be employed to examine the regulation of airflow and its mechanical determinants: pharyngeal critical pressure (Pcrit) and upstream nasal resistance (RN). In Specific Aim #1, the influence of alterations in upper airway structure on airflow and its mechanical determinants in (a) the presence and absence of upper airway muscle activation, and (b) after surgical reconstruction of the upper airway will be examined. In Specific Aim #2, the effect of phasic neuromuscular activation of the upper airway on flow and its mechanical determinants will be determined. In Specific Aim #3, the effect of alterations in reflex control will be determined by examining the chemical and mechanical reflex control of upper airway neuromuscular activity, airflow, and its mechanical determinants. In each specific aim, experiments in the isolated canine upper airway will examine each of the factors outlined above to elucidate basic mechanisms controlling the mechanical, phasic neuromuscular activation, and reflex control of the upper airway. These animal experiments are designed to test present concepts believed important in the regulation of airflow in the upper airway, and to facilitate the development and application of new approaches to treating patients with obstructive sleep apnea. Specialized recording techniques for sleep, pressure, flow, and EMG activity will be employed and their relationships to the mechanical determinants of flow will be determined.